4E7W

Structure of GSK3 from Ustilago maydis

Summary for 4E7W

• Entry DOI: 10.2210/pdb4e7w/pdb
• Descriptor: Glycogen Synthase Kinase 3 (1 entity in total)
• Functional Keywords: gsk3, kinase, ptyr195, transferase
• Biological source: Ustilago maydis (Smut fungus)
• Total number of polymer chains: 1
• Total formula weight: 44797.78

Authors

Gruetter, C.,Rauh, D. (deposition date: 2012-03-19, release date: 2012-05-16, Last modification date: 2024-10-30)

Primary citation

Grutter, C.,Simard, J.R.,Mayer-Wrangowski, S.C.,Schreier, P.H.,Perez-Martin, J.,Richters, A.,Getlik, M.,Gutbrod, O.,Braun, C.A.,Beck, M.E.,Rauh, D.
Targeting GSK3 from Ustilago maydis: Type-II Kinase Inhibitors as Potential Antifungals.
Acs Chem.Biol., 7:1257-1267, 2012

PubMed Abstract: Protein kinases are key enzymes in the complex regulation of cellular processes in almost all living organisms. For this reason, protein kinases represent attractive targets to stop the growth of eukaryotic pathogens such as protozoa and fungi. However, using kinase inhibitors to fight against these organisms bears several challenges since most of them are unselective and will also affect crucial host kinases. Here we present the X-ray structure of glycogen synthase kinase 3 from the fungal plant pathogen Ustilago maydis (UmGSK3) and its inhibition by type-II kinase inhibitors. Despite the high sequence homology between the human and the fungal variant of this vital kinase, we found substantial differences in the conformational plasticity of their active sites. Compounds that induced such conformational changes could be used to selectively inhibit the fungal kinase. This study serves as an example of how species-specific selectivity of inhibitors can be achieved by identifying and addressing the inactive state of a protein kinase. In addition to this, our study gives interesting insights into the molecular plasticity of UmGSK3 by revealing a previously unknown inactive conformation of this important kinase family.

PubMed: 22545924
DOI: 10.1021/cb300128b

Experimental method

X-RAY DIFFRACTION (3.3 Å)